Digestive and Liver Disease最新文献

The PRODIGE 85-FFCD 1804-KANALRAD trial has been designed as a multicenter, randomized, open-label, phase III trial to compare the efficacy of induction chemotherapy (4 cycles of modified DCF: Docetaxel, Cisplatin, and 5-Fluorouracil) prior to standard chemoradiotherapy (CRT) versus standard CRT alone for histologically proven locally advanced squamous cell carcinomas of the anal canal (SCCA), either T3-4 or with lymph node involvement and no metastases. The primary endpoint is event-free survival at 2 years. Secondary endpoints include disease-free survival, complete response rate, patient quality of life, and monitoring of treatment-associated toxicities. A safety analysis is planned after enrollment of the 20 first patients in the experimental arm to ensure the feasibility of CRT after induction chemotherapy. In addition, genetic and epigenetic studies from tissue and circulating DNA will be conducted to assess their prognostic or predictive value. Overall, 310 patients will be recruited in France and will be followed for 3 years after randomization.

Background: Primary intestinal B-cell (IBCL) and T-cell (ITCL) lymphomas are rare and poorly characterized entities.

Aim: To compare clinical features and survival outcomes of IBCL and ITCL.

Methods: We conducted a multicentre, retrospective study including patients diagnosed with primary intestinal lymphoma between 2001 and 2024. Clinical and laboratory variables were analysed using univariate and multivariate logistic regression. Discriminatory accuracy was assessed through ROC analysis. Overall survival was estimated with Kaplan-Meier curves.

Results: Ninety-four patients (41 IBCL and 53 ITCL) were included. IBCL were more frequently diagnosed at Lugano stage I (90% vs 5.7%; p<0.01) and showed markedly lower lactate dehydrogenase and β2-microglobulin levels compared with ITCL (p<0.01). Coeliac disease (CD) was strongly associated with ITCL (p<0.01). In multivariable analysis, CD and biomarker levels independently differentiated IBCL from ITCL, with excellent model discrimination (AUROC 0.95). Median follow-up was 56 months for IBCL and 12 months for ITCL. IBCL demonstrated significantly greater survival (HR 0.21; log-rank p=0.01).

Conclusions: IBCL and ITCL exhibit distinct clinical and prognostic profiles, with IBCL showing more favourable clinical profile and better survival. Tailored diagnostic and therapeutic approaches that reflect the divergent behaviour of these lymphomas are urgently needed.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of liver conditions, primarily driven by metabolic factors and characterized by steatosis. Extracellular vesicles and particles (EVPs) are emerging as biomarkers for liver diseases as they reflect the state of their cells of origin and carry molecular cargo that can influence disease progression. We aimed to explore the role of EVPs with MASLD progression, smoking impact and EVPs effect on macrophages.

Methods: We analyzed EVPs using nanoparticle tracking analysis, transmission electron microscopy and flow cytometry. Cytokine expressions were quantified in EVPs-exposed macrophages.

Results: We showed that EVP number is higher in patients with steatohepatitis and they were correlated with the severity of liver inflammation and steatosis, as well as with biological markers. In particular CD63⁺-ASGR1⁺-EVPs were notably more prevalent in blood of patients with steatohepatitis. Active smoking further increased EVP numbers and CD63⁺-ASGR1⁺-EVPs in MASLD patients. Functionally, exposure of macrophages to CD63⁺-EVPs from MASLD patients induced TGF-β and TIMP-1 secretion.

Conclusion: This study highlights the potential of EVs as biomarkers for MASLD progression and their role in mediating disease mechanisms via intercellular communication, notably by their potential to contribute to fibrogenic signaling. Although exploratory, the study also highlights the potential impact of the exposome, particularly smoking, on MASLD pathogenesis.

Background: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder with multifactorial etiology, including genetic components. Despite numerous genetic association studies (GAS), the role of specific gene polymorphisms in GERD susceptibility remains unclear due to inconsistent findings.

Aims: To systematically review GAS on GERD and conduct a meta-analysis to evaluate the association between specific gene polymorphisms and GERD risk.

Methods: A systematic review of PubMed, Cochrane, ScienceDirect, Scopus, DisGENET, GWASCatalog, and HuGE Phenopedia databases (2012-2024) was conducted to identify GAS for GERD. Meta-analytical methods were used to synthesize the results.

Results: 21 GAS, including 27,783 GERD patients and 83,857 controls, were analyzed, focusing on 132 polymorphisms across 105 genes. Meta-analysis of seven studies revealed a significant association between GNB3 rs5443 C > T and increased GERD-like symptom phenotypes (ORp = 2.24, 95 % CI: 1.56-3.21), suggesting a dominant genetic model. No significant associations were found for TNF, IL1B, or CYP2C19. Heterogeneity and potential bias were observed in some analyses, necessitating cautious interpretation of the findings.

Conclusion: The findings support a robust association between GNB3 rs5443 C > T and susceptibility to GERD-like symptom phenotypes, suggesting a potential genetic predisposition. Additional large, well-characterized studies using standardized GERD definitions are needed to validate these results and elucidate the broader genetic landscape of the disease.

Background and aims: Living donor liver transplantation (LDLT) helps address organ shortages but remains complex, particularly in Western countries where deceased donor liver transplantation (DDLT) is preferred. This study evaluates improvements in LDLT outcomes over time for both donors and recipients.

Study design: A single-center retrospective analysis from 2001-2023 including two periods: P-ONE (2001-2003, 36 cases) and P-TWO (2020-2023, 27 cases). Donor surgery after October 2022 marked the shift to a full robotic approach. Recipient procedures preserved the retro-hepatic vena cava, with standard vascular and biliary reconstruction. Comparisons include demographics, complications, and survival.

Results: P-ONE donors were younger (median age 32 vs. 46, P=0.003), while P-TWO recipients were older (63 vs. 56 years, P=0.005) with more comorbidities. P-TWO had more cases of hepatocellular carcinoma and low-MELD cirrhosis. Donor safety improved in P-TWO, with similar major complication rates (14% vs. 11%). Recipients in P-TWO had fewer severe complications (7% vs. 81%, P<0.001) and better 3-year graft survival.

Conclusions: Advances in patient selection, minimally invasive surgery, and perioperative care have significantly improved LDLT outcomes. Despite persistent biliary challenges, LDLT remains a promising solution for end-stage liver disease and liver cancer.